A Study of the Combination Vorinostat With Lenalidomide, Bortezomib and Dexamethasone for Patients With Newly Diagnosed Multiple Myeloma

• Register: ClinicalTrials.gov
• Last refreshed on: 15 November 2021
• Main ID: NCT01038388
• Date of registration: 07/07/2009
• Prospective Registration: Yes
• Primary sponsor: Emory University
• Public title: A Study of the Combination Vorinostat With Lenalidomide, Bortezomib and Dexamethasone for Patients With Newly Diagnosed Multiple Myeloma
• Scientific title: A Phase I Trial Evaluating the Safety and Efficacy of Vorinostat (Zolinza ®) + RVD (Lenalidomide {Revlimid ®} + Bortezomib {Velcade ®} + Dexamethasone) for Patients With Newly Diagnosed Multiple Myeloma
• Date of first enrolment: January 15, 2010
• Target sample size: 30
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01038388
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Jonathan Kaufman, MD
• Affiliation: Emory University

Key inclusion & exclusion criteria

Inclusion Criteria:

- Multiple Myeloma Diagnosis: Subject was previously diagnosed with multiple myeloma
based on standard diagnostic criteria or by the new International Myeloma Foundation
2003 Diagnostic Criteria (ALL 3 REQUIRED):

1. Monoclonal plasma cells in the bone marrow > 10% and/or presence of a
biopsy-proven plasmacytoma.

2. Monoclonal protein present in the serum and/or urine.

3. Myeloma-related organ dysfunction (1 or more).

- [C] Calcium elevation in the blood S. Calcium >10.5 mg/l or upper limit of
normal{}.

- [R] Renal insufficiency S. Creatinine > 2 mg/dl{}.

- [A] Anemia Hemoglobin < 10 g/dl or 2 g < normal{}.

- [B] Lytic bone lesions or osteoporosis.

- Patient must not have been previously treated with any prior systemic therapy for the
treatment of multiple myeloma.

- Prior treatment of hypercalcemia or spinal cord compression with corticosteroids
does not disqualify the patient (the dose should not exceed the equivalent of 160
mg of dexamethasone in a 2 week period).

- Bisphosphonates are permitted

- Patients treated with local radiotherapy with or without concomitant exposure to
steroids, for pain control or management of cord/nerve root compression, are eligible.
One week must have lapsed since last date of radiotherapy, which is recommended to be
a limited field. Patients who require concurrent radiotherapy should have entry to the
protocol deferred until the radiotherapy is completed and one week have passed since
the last date of therapy.

- Voluntary written informed consent before performance of any study-related procedure
not part of normal medical care, with the understanding that consent may be withdrawn
by the subject at any time without prejudice to future medical care.

- Females of childbearing potential (FCBP)† must have a negative serum or urine
pregnancy test with a sensitivity of at least 50 milli-international unit (mIU)/mL 10
- 14 days prior to therapy and repeated again within 24 hours of prescribing
lenalidomide and must either commit to continued abstinence from heterosexual
intercourse or begin TWO acceptable methods of birth control, one highly effective
method and one additional effective method AT THE SAME TIME, at least 28 days before
she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men
must agree to use a latex condom during sexual contact with a FCBP even if they have
had a successful vasectomy. All patients must be counseled at a minimum of every 28
days about pregnancy precautions and risks of fetal exposure.

- Age = 18 years at the time of signing Informed Consent.

- All necessary baseline studies for determining eligibility must be obtained within 21
days prior to enrollment.

- Subject has a Karnofsky performance status of = 60.

- Subject must be able to adhere to the study visit schedule and other protocol
requirements.

- All study participants must be registered into the mandatory RevAssist® program, and
be willing and able to comply with the requirements of RevAssist®.

- Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients
intolerant to acetylsalicylic acid [ASA] may use warfarin or low molecular weight
heparin).

Exclusion Criteria:

- Patient has = Grade 2 peripheral neuropathy on clinical examination within 14 days
before enrollment.

- Renal insufficiency (serum creatinine levels > 2.5 mg/dL).

- Subjects with evidence of mucosal or internal bleeding and/or platelet refractory
(i.e., unable to maintain a platelet count = 50,000 cells/mm³).

- Subjects with an absolute neutrophil count (ANC) < 1000 cells/mm³. Growth factors may
not be used to meet ANC eligibility criteria.

- Subjects with a hemoglobin < 8.0 g/dL.

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 2 x upper limit
of normal (ULN).

- Concomitant therapy medications that include corticosteroids (except as indicated in
inclusion criteria).

- Myocardial infarction within 6 months prior to enrollment or has New York Heart
Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe
uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
ischemia or active conduction system abnormalities. Prior to study entry, any ECG
abnormality at screening has to be documented by the investigator as not medically
relevant.

- Clinically relevant active infection requiring intravenous antibiotics.

- Serious co-morbid medical conditions such as chronic obstructive or chronic
restrictive pulmonary disease, and cirrhosis.

- Any condition, including laboratory abnormalities, that in the opinion of the
Investigator places the subject at unacceptable risk if he/she were to participate in
the study.

- Prior malignancy (within the last 3 years) except for adequately treated basal cell or
squamous cell skin cancer, in situ cervical cancer, in situ breast cancer, in situ
prostate cancer or if the expected survival from other malignancy is greater than 90%
at 5 years.

- Female subject is pregnant or breast-feeding.

- Serious medical or psychiatric illness likely to interfere with participation in this
clinical study.

- Uncontrolled diabetes mellitus (Fasting Blood Sugar > 400 despite medical treatment).

- Hypersensitivity to acyclovir or similar anti-viral drug.

- Known history of POEMS syndrome (plasma cell dyscrasia with polyneuropathy,
organomegaly, endocrinopathy, monoclonal protein (M-protein) and skin changes).

- Known HIV infection .

- Known active hepatitis B or C viral infection.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Multiple Myeloma

Intervention(s)

Drug: Dexamethasone

Drug: Bortezomib

Drug: Vorinostat

Drug: Lenalidomide

Primary Outcome(s)

To determine the maximum tolerated dose (MTD) and recommended phase II doses (RP2D) of vorinostat in combination with lenalidomide, bortezomib, and dexamethasone. [Time Frame: Every 3 weeks]

Secondary Outcome(s)

Efficacy by standard myeloma measurements (SPEP, UPEP [urine protein electrophoresis], bone marrow) [Time Frame: Every 3 weeks]

Secondary ID(s)

IRB00017528

1591

RV-MM-PI-0420

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Merck Sharp & Dohme Corp.

Celgene Corporation